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Author
Topic: Starting VRX496 (Read 50080 times)

I don't know that the whole study will be followed for 15 years. I do know that each person in the study will be followed for 15 years. Does that mean the study if approved will take 15 years? Not sure but I would sure hope not.

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there is billions of revenue and millions to anyone who discovers something like this, the 15 years is just protocol to show how compassionate and careful they are being with test subjects. If it worked like gang busters it would be put on market much like many things are, and if some have side effects they would look into that then...the 15 years is just so they do their job, this is very new new science and they must follow the law,

if it works i see many people who are failing other drugs to be put on this, Dr. do not want to have someone die if there is something that will keep them alive so seems like the first would be, failing other combos

so that is in a way good because they can go thru compassionate use, which has fewer restricitions

also i want to state emphatically

gene therapy will triumph over all viral resistance for the reasons i outline above

if you carefully watch the animations and understand

you will see what i mean

the sissors that cut things up inside cells are very efficient, think how good skin grows and falls off, and this gene therapy is kind of like giving the nucleus a message to ... hey cut up this dna that isnt suppose to be in here...

Some patients maintained outcomes for three years, and genetically modified CD4 T cells remain in circulation.

-convenient for patients by eliminating the need for multiple daily pills.

Jun 1 2007 (Vol. 27, No. 11)

http://www.genengnews.com/articles/chitem.aspx?aid=2119VRX496 suppressed viral loads and restored the immune system responses in chronic HIV patients. This is an important milestone in the development of what we believe could be the next generation of HIV therapy, says Riku Rautsola, Ph.D., president and CEO of VIRxSYS.

VRX496 is the first and only lentiviral vector therapy approved by the FDA for clinical trials. The backbone of VRX496 consists of a genetically engineered version of HIV in which all the infectious components are removed and replaced with the therapeutic payload a long antisense sequence that targets the HIV envelope protein and cripples the virus.

Preclinical studies show that HIV is unable to mutate around VRX496. which should prevent the formation of resistant strains. We have seen no resistance develop to our therapy in vivo or in vitro.

VRX496 is an autologous therapy that uses a patientís own cells.

The goal is to repopulate a patientís immune system with genetically engineered cells that promote immunity against HIV and prevent the progression to AIDS. Although not a cure, VRX496 could improve the quality of life for HIV patients by bringing viral loads down to low levels.

In a Phase I trial, five chronic HIV patients, who had failed to respond to multiple standard antiretroviral drug regimens, received one infusion of VRX496. All patients showed stable or decreased viral loads as well as stable or increased immune responses to HIV antigens. Four of the five had stable or increased CD4 T cells. Some patients have maintained these positive outcomes for up to three years, and the genetically modified CD4 T cells remain in circulation.

A Phase II study is under way in 40 chronic HIV patients to further establish the safety and tolerability of VRX496 and to determine the optimal dose.

Current anti-HIV drugs are small molecules that are highly toxic. Because HIV mutates rapidly, it often becomes resistant to conventional drug regimens taken by patients. VIRxSYSí alternative gene therapy is designed to block all the mutation sites on HIV, preventing resistance. Thus VIRxSYS says that VRX496 overcomes the problems of toxicity and resistance.

VRX496, which is intended as a short-term therapy that offers long-term benefits, may be more convenient for patients by eliminating the need for multiple daily pills.

privately held VIRxSYS has a unique financing model. A group of private shareholders provides funds, and the company has not had to rely on traditional venture capital. ďWe are fortunate to have loyal shareholders who finance us,Ē Dr. Rautsola says.http://www.genengnews.com/articles/chitem.aspx?aid=2119 read the full article it is great...Jun 1 2007 (Vol. 27, No. 11)

In a Phase I trial, five chronic HIV patients, who had failed to respond to multiple standard antiretroviral drug regimens, received one infusion of VRX496. All patients showed stable or decreased viral loads as well as stable or increased immune responses to HIV antigens. Four of the five had stable or increased CD4 T cells. Some patients have maintained these positive outcomes for up to three years, and the genetically modified CD4 T cells remain in circulation.

Thanks Biz for the great info and thanks again Appleboy for doing this - we are ALL grateful.

I remember reading a pretty extensive discussion in the old forums where the 5th guy of the 'four of five' mentioned above was posting a lot and was pretty pissed about some of the ways he had been treated and also that it looked like he wouldn't be allowed to be in future studies, which seemed pretty insane. Again, I can't find the link, so if anyone knows how to get to those forums, it might be interesting and helpful to read up on it and maybe contact him too - especially for Appleboy.

I'm also still dying to know the outcome of the Johnson/Tibotec gene therapy trial that was supposed to be finished in Jan. From the article in the SF chronicle, that one sounded extremely promising, yet there has been no mention of it anywhere of late - at least that I've seen.

Thanks again Apple - we're following your every post with bated breath!

Bim, You are such a sweetie! Thanks for all your information. NYC thanks for support it is much appreciated. The first meeting for the trial is coming up soon. I think I am kinda excited but kinda nervous at the same time. The whole anal biopsies have me in a bit of a tizzy. I don't like being naked in an office around strangers having things stuck up my butt. If I can get past the way I feel about that I think I will be ok.

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i am thinking about this and i am going to do a first draft here, although anyone who reads my posts knows they are all first drafts un-corrected or spell checked... ohh i just noticed the spell check button on here for first time ever, well that is i guess what it means being only a few months after diag.

here is my thoughts

how do you get a giant ocean liner cruise ship to stop

how do you get a giant ocean liner cruise ship to stop and go in opposite direction

it takes so so much time, well this is how i feel we are all, in a ship

the ship is haart, and meds, and toxic meds, and side effects, the Dr.s are driving or the insurance companies or a combo of many powerful groups

remember when all there was was azt, well a few crazy dr.s started giving guys multiple meds and some guys even shared and had parties where they would all take each others meds, i think they put them in a bowl

i am not advocating any of that, and i am totally pro haart under 350 and i am sure treatment interuptions must only be done in certain circumstances so i am not against haart

anyway remember that period between 1990 and 1996 and really even 1998 when haart was widely accepted and given to most in usa, and then it took time to figure out why some were not responding perfectly, most did great

well

that period in the 1993 to 1998 is kind of like now

i would like to boldly say, i believe that the virsys VRX496 is so dramatic in its results and so powerful and as the article that thier scientists wrote the meds are toxic, well i have never yet been on meds and i am holding on to every t cell, trying to go as far into future before starting meds but i will start when necessary

anyway

the virsys VRX496 is so dramatic in its results adn so hopeful and such, even though the first trial is small, lets say it is 12 or 22 months and the group of guys and appleboy and such tell us how great they are doing

how long how hard will it be how long will it take to slow this giant cruise ship of haart and meds, and Rx and pills, how long will it take until dr.s are comfortable until fda approves until compassionate use kicks in

i mean lets do a million man march from washington TO PHILLY that would be dramatic or at least all drive there

i dont know perhaps i am talking out of fear but really i cannot accept one more day of hiv poz guys dying, i have been watching this channel of suffering for 25 years as many have, i was neg. 2 years ago... i have lost so so many friends lovers, mentors, etc... and

well it seems so close it seems so hopeful

i mean the article the way it said June 1, 2007 while its still in may, i know mags do that , but it seemed almost like it was coming out of the future

we need to meet with congressmen now

barney frank -- can someone call him or email him this info

about virsys VRX496

ok lets do a thought experiment,

day one -- what does it take to get compassionate use approved for a GENE THERAPY -- see that is something that has never been done before!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

to ramp up the treatment of a gene therapy -- that has never been done before!!!

is there any gene therapy that is currently fda approved?

does it take a different path than drug approval?

this has never been done before...

the time lag, of the 15 to 25 people who die every day in USA from HIV and its related diseases and causes

what do we need to do to get an expanded 3rd phase trial

after compassionate use is approved how long does it take to get to next step

is there something availble

i mean ... what does it take to give this virsys VRX496 -- as compassionate use to many people

keep taking haart though cause that is important and even vrx496 can come later

While they check on your CD4, will they also check your PD-1 or other index that people believe is also related to AIDS progressing? If not, would you mind requesting for that data?

Correct me if I am wrong, but I believe you are on Haart now. What was your lowest CD4 before? and When was it? And your Haart combination is?

Sorry for intriguing question like this. Since some paper said CD4 is not the only index that shows the result. I believe other index like PD-1 is also very important. And the medicine you take may have some effect on "penetration rate" of VRX496. Therefore, I would appreciate the disclosure.

PD-1 levels are only measured so far in animal and human clinical trials it is not available yet to doctors, in clinical practice, only in Universities and Studies, it parallels almost exactly the CD4 count numbers but recent discoveries in last few weeks, show that it actually may PREDICT the rapid fall of CD4s, and come first and be actually the cause of the rapid fall of CD4s. for example, the CD8 cell has pd-1 receptor, when the pd-1 is low and not turned on the CD8 does just fine and fights off hiv every day, this goes on for years, then some trigger or chemical causes the pd-1 switch (there are millions on every CD8) to be turned on to high.

pd-1 high HIV specific CD8 cell is what it is called

when these switches get turned on then the CD8 becomes disfunctional and disoriented and does not work well fighting off and suppressing the hiv virus, which it had done so well for the first 5 to 19 years of the disease of hiv.

when this happens, and science in last weeks feel it is preceeds the fall in cd4 obviously because once the cd8 stop fighting the hiv off the cd4s are cascading and more and more get infected

so once the cd8 is not supressing the infection that is when the cd4s drop from say 300 to 200 to 100 to 30, and this sometimes can happen quickly

one week ago they discovered that, it is the number of pd-1 switches that are turned on or high in the HIV specific CD8 cell that determines if the cd8 becomes unable to fight, in other words if 90% of the pd-1 on outside of one cd8 cell are still low, then the cd8 works just fine, but if, say 80% are high then the cd8 doesnt work.

also 2 months ago chinese at univ beijing proved that all LTNP all long term non progressors have a pd-1 that is different, and somehow stays low, so the cd8s never get turned off,

PD-1 is best not to be called Programmed Death anymore, because that was a Mis-naming that was done at the time of discovery of pd-1 ten years ago or 12 i forget, it is bad idea and science is calling it other things now because when they first isolated and noticed the receptor it was on cells that were under-going a natural process called cell apotosis or cell death or cell go by by, many times when cells are not used anymore the body sends a signal to the cell to get rid of itself so new cells can take overwhen they discovered PD-1 they called it Programmed Death-1 because when a cell was dying they noticed that there was this chemical switch and they made the mistake of thinking this switch causes the cell death, it does not it was present because

before the cell dies the body turns off the functioning of the cell first -- and now they discovered that that is what the receptor or switch does it tells the cell to stop functioning to become exhausted

so dont be frightened by the name

it was a mis-naming because they thought it was involved but now they knowesp. for hiv disease, that the pd-1 controls a path that tells the CD8 cell

hey you are done with fighting this viral infection, go to sleep or become exhausted or become un functioning

remember when you get a cold or a flu the body stages a big immune response and you can feel it as a wave of attack of the immune system as it kills the bugs, then you feel the immune system backing off and cleaning up and checking things to see if the infection is gone then sometimes if the body thinks that the infection is still there it attacks again sends soldiers out and then retreats and puts the soldiers away and cleans up all the toxins that are released by the fight

this is what pd-1 is for, it is part of signalling to tell the cd8 killer cells, hey things are taken care of, go away not needed anymore, the problem with hiv disease is

it is a trick the infection is hiding inside the very cells that are part of the immune system so the immune system managers get all confused and eventually they stop fighting the hiv

remember our bodies do a great job for 5-11 years and some times 20 years without meds, the cd8s are doing the fight 50 billion viruses a day and killing them and sweeping up the mess that is made in the war

so

then as i wrote above

so the real name could be Programmed Exhaustion or Programmed disfunction

and that is also what is so cool about a new discovery about pd-1 in nov or dec 2006

that if they block the pd-1

THE CD8 CELLS are NOT DEAD OR PERMANTENTLY turned off, all they have to do is block the PD-1 and the CD8 wakes up and is fully fuctional and can fight HIV and the infection just like the first 3-9 years of the infection

this was just discovered i think dec 2006

a big breakthru becuase they didnt know if the cd8 SYSTEM was so messed up by the pd-1 that it wouldnt work in the future at all and no treatment could repair it

and they found wow, the cd8s are there in numbers they function and they can come back strong as before

this is how apes cats etc fight thier HIV they never get sick cause the body cd8 never get exhausted

without meds

but i am most excited about the VRX496

this is fighting

FIRE WITH FIRE

fighting the HIV with a modified hiv that has some gene sizzors inserted into it

Here's an older (2005) story about VRX496. What's interesting is that it gives a sort of preliminary timeline leading towards approval (if everything goes as planned, which is, granted, a big 'if'). Anyway, they appear to be a little bit behind schedule, although someone posted here that Phase III was a possibility for this year. In any event, this is what it says:

'But Rautsola also said the company is continually looking for a partner, and he expects VIRxSYS to team with another company before beginning Phase 3 trials by 2007. He said if all goes well, Phase 3 trials could be completed in early 2009, and a product could go on the market later that year, adding that if the FDA approves an accelerated regulatory path the product could get to large patient populations before that.'

This is an interesting study and goodluck to you appleboy. Participation by people like you in these trials ulitmately helps he greater community and to me it is very selfless. So I thank you.

The PD-1 conversation has been occurring for sometime. I'm not sure if I'm derailing this thread or not but the PD-1 receptor and it's cognate ligands PD-L(1) and PD-L(2) is a regulator of immune cell function and is expressed primarily on activated immune cells and is meant to maintain homeostatis of the cells in the body (i.e. a balance between activated and inactivated cells). The programmed death part refers to the conference of susceptibility of cells expressing PD-1 to programmed cell death or apoptotic signals (such as by Fas-ligand). Programmed cell death is merely an organized and fairly well characterized process of cell death mediated by a signalling event. PD-1s upregulation and interaction with its ligands inhibits activated immune cell functioning (e.g. responsivness to certain cytokines, production of cytokines...). It provides and important function in non-chronic infections of ensuring the immune system does not go crazy. In chronic infections, constant activation of cells, constant upregulation of inhibotry signalling mechanisms such as PD-1 and CTLA4 result in functional cell exhaustion and ultimate dysfunction.

Blocking of PD-1, suppression of infection through successful HAART and even treatment with stimulatory ytokines such as IL-2 could be good future therapies. Also, monitoring of P-1 levels couldl be a good predictor of things going south....

hi, i'm newplease be gentle.i have been following this company since last year. it sounds promising i'm so happy the results are in.i'm curious about the risk factors i hear they changed somthing to reduce the risk of cancer...do you know what they did. please keep us posted. i hear there is another group possible 40 people in this study does this last for another two years?............... i think it would be a great treatment option! however do you think in the next few years you can see people hooked up to a machine for a few hours and then be on their merry way??/ it would be a nice thought wouldn't it!oh i live in Canada...i'm just really curious.

hey jake that sounds interesting..so they are a little behind in phase 3 2007-2009 .a product to get out by 2009 interesting.thats cool so i guess it would take awhile to reach Canada wouldn't the drug companys feel threatned i wonder?

I would want nothing but success for this!I also have the same question either it will be expensive or can you imagine millions of people lined up to a dialasis machine i america? ican't mnot enough machines? too expensive? hmmm only for the rich don't know still in trial 2questions hmmm

hey jake that sounds interesting..so they are a little behind in phase 3 2007-2009 .a product to get out by 2009 interesting.thats cool so i guess it would take awhile to reach Canada wouldn't the drug companys feel threatned i wonder?

Yeah, it appears that they may be a bit behind schedule unless a Phase III trial starts at the end of the year. I wish I had more information about the trials.I'm also in Canada, incidentally, and there seems to be a 6 month-one year lag time in therapy approval between the United States and Canada (and I'm presuming the European Union). However, if this were really amazing, perhaps the lag time would be reduced. Also, Appleboy posted that the company seems to think that local centres (maybe current clinics and HIV/AIDS service organizations?) would be set up for dialysis. Since the procedure wouldn't be a frequent one (let's say once a year, once every other year, or...ideally, once ever!), I don't know how backed up the centres would be.

Whoa! I go on vacation and I loose track of this thread! Tomorrow is the day for my intake into the VRX496 Study. I am excited yet quite nervous how I am going to fit all this and my busy work schedule together. Power I sent you answers to your question via a reply to your private message. JP thank you for the kind words and the nice information. Thanks Stand for the prayers. I really hope and pray this stuff works and this can help the masses. Power the price may still be cheaper than the cost of meds if this works. So, keep an eye out on my blog and here I will try to keep you updated as to what is going on. My counts as of my last lab work was VL Undetectable with the ultra sensitive test and my CD4 was 517/25% . I hope that answers all the questions and I did not leave anyone out.AppleBoyhttp://appleboyde.wordpress.com

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so a cd4 cell has a short life span. how does modified cells live up to a year or more in the body? memory cells produce more in the bone marrow???don't know how? but these guys were off meds for up to three years. so some how the cells must produce. right?

I am exhausted! I got up at 4:50 this morning to get ready to go to UPenn for my intake into VRX496. I was on the road by 5:45. I donít like traffic so I decided that if I left that early the traffic would not be as bad. It was not all that bad thank goodness. The visit went great I met the study intake coordinator who is just awesome and my regular ID Dr ended up doing my physical so it was great to get to see her for a few minutes. They took 10 or so vials of blood for lab work. They are doing all kinds of tests including making sure I donít have a antibody for the vector which carries the VRX changed HIV. They also are doing a Viral Load test that goes down to 30 (I think this the number she said and it is lower than the currently used Ultra Sensitive Viral Load Test. So now I wait. If I have the antibody for the vector I am out of the study. Which means my immune system will attack the VRX changed CD4 cells instead of accepting them which would defeat the purpose of VRX496. Next will be if my Viral Load is not undetectable with the Super Ultra Sensitive test then I am out of the study. So my fingers are crossed that my VL is undetectable and I donít have the antibody to the vector. We talked a lot about the procedures and signed what felt like tons of paperwork. The whole goal is to make sure I am safe and that everything goes correctly. This made me feel so good. My safety is my most important priority. I pray and hope this stuff works and that I can be fully accepted into the study and if it does not work I just want to be safe which I donít think will be a problem. I should know in a few weeks for sure and I have the date for the first CD4 cells collection which is July 2. So the waiting begins!

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I got a call that my Viral Load tests where back and they are 129 it has to be less than 30 to enter the study. The viral load is not undetectable meaning right now I cannot be in the study. So tomorrow I am going to give another tube of blood for them to do another VL test. I am hoping this was just an odd spike. If it is not my ID doctor wants me to change around my medications. This will suck as it means one or two more co-pays a month. But if we change meds we I can try again for the study in 4 weeks. So lets hope it was just a blip if not life goes on we do what we have to do! Blah, I am rather disappointed at this current moment but who knows what the next VL test is going to look like in a few days.

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Apple dear, on the other side of the ocean, which we name Europe, people r not that muchly into MAC...so from two different worlds we r, first the PCs didn't match. and i know see that u might not get into the test...well, i still have not changed my mind at all, i want a brave husband like u!consider it thoroughly dear apple, condiser it thoroughly... :-D

Since I had another VL draw on Tuesday I am hoping to hear either tomorrow or Friday what it was. I am hanging in here just doing the usual waiting and researching the drugs my dr will change me to if it is indeed not under 30. If the med change happens I will have to wait to try and reenter the study after 30 days of being on the new meds. I will keep everyone up on what is going on soon as I know and can get to a computer to type it out. Next, I want to thank everyone that has sent kind words and suggestions. That honestly makes me feel good and it warms my heart. So here is to better news I hope later this week!Bill

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DAMN IT! I just got back the second VL test results and it is 103. The my VL has to be below 50 to get into the study. I got an e-mail just after the one about the results from my doctor at UPenn and she said lets change meds and then attempt to enter the study again in 30 days. So here is what has been suggested she is waiting till Wednesday's community meeting to see what the other doctors think.

1. Drop Sustiva component of Atripla and replace it with Atazanavir boosted with Ritonavir so I would be on Atazanavir, Ritonavir and Truvada.2. Keep Atripla and add Abacavir.

I am leaning towards 2 since that would only add one co-pay to what I am paying now and my VL is very low. So right now I am sitting and waiting for word from my doctor as to what we are going to do as far as meds once I start I will try to enter the study again in 30 days.

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Hey AppleboyThanks for keeping us posted. Keep your chin up! I really appreciate all the candid info. As for your drug choices, I will just say that I have been on the reyataz (300) boosted with Norvir plus Truvada for 6 mo, and I have been pretty happy with it, or at least as happy as I can be knowing that I have to take something. Almost no side effects (a bit of the runs for a few days, but no problem now as long as I eat enough) and none of Sustiva's craziness. I went below 250 in 1 month then <50 after 2. And I started out with VL over 250,000! I would urge you to screw the co-pay and do what you and your Dr. think is best. It's only money, after all...